This proposal by the University of North Carolina Project based in Lilongwe, Malawi aims to characterize safety, durability, ART resistance, and clinical outcomes for mothers and infants exposed to the efavirenz-based Option B+ regimen for Prevention of Mother to Child Transmission (PMTCT) and HIV treatment in Malawi. Option B+ is an innovative strategy pioneered within Malawi that provides universal life-long ART (tenofovir/lamivudine/efavirenz: TDF/3TC/EFV) for pregnant and breastfeeding women. Importantly, Option B+ was adopted largely based on programmatic need and has not been directly studied in clinical trials. The safety of a TDF/3TC/EFV based regimen used during pregnancy has not been systematically evaluated. Notably, TDF/3TC/EFV has a low barrier to resistance such that women and infants may be particularly susceptible to resistance in the event of sub- optimal retention or adherence. Hence, the durability of the regimen may be sub- optimal over time and second line therapy may be required for subsequent pregnancies. Now, with over 2 years of follow-up time in the Option B+ program in Malawi, we are in a unique position to explore these questions related to treatment failure, in addition to the effectiveness and safety of second line therapy with Atazanavir/ritonavir among women presenting with subsequent pregnancies in the program. The proposed study will take place at four high volume antenatal sites within Lilongwe, Malawi where UNC project and the Baylor Tingathe Program (who will be collaborating on this study) have established infrastructure. Using a prospective cohort study design, we will enroll newly identified HIV infected women at the first antenatal visi and follow maternal and infant outcomes through year 3 post-delivery. Among women with subsequent pregnancies in the program, we will measure the prevalence of virologic failure and assess the need for second line therapy. In the event of failure, we will evaluate the safety of Atazanavir/ritonavir during pregnancy. Among defaulters of the program with subsequent pregnancies, after resumption of first line therapy, we will evaluate for early treatment failure and determine resistance profiles associated with this population. For all cohorts, key outcomes will include DAIDS grade 3 or 4 events, adverse pregnancy and birth outcomes, HIVRNA suppression, maternal and infant drug resistance, and infant neurologic development. Our research plan has been carefully developed to be complementary to existing program and research activities and anticipates the next critical questions that can only be answered with a more mature Option B+ program. Hence, our ability to answer these questions now will inform other programs as they embark on an Option B+ program.